The orexins and their receptors are involved in the regulation of arousal and sleep-wake cycle. Clinical investigation with almorexant has indicated that this dual OX antagonist is efficacious in… (More)

The term 'pharmacological promiscuity' describes the activity of a single compound against multiple targets. When undesired, promiscuity is a major safety concern that needs to be detected as early… (More)

The superfamily of G protein-coupled receptors (GPCRs) is the largest and most diverse group of transmembrane proteins involved in signal transduction. Many of the over 1000 human GPCRs represent… (More)

Potency with potential: 2-Phenoxy-nicotinamides were identified as potent agonists at the GPBAR1 receptor, a target in the treatment of obesity, type 2 diabetes and metabolic syndrome. Extensive… (More)

In this study, we show that compound 3 (osanetant) binds with a pseudoirreversible, apparent noncompetitive mode of antagonism at the guinea pig NK(3), while it behaves competitively at the human… (More)

From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar… (More)